Oncologic Drugs Advisory Committee

1
C

• Oncologic Drugs Advisory Committee
• Bethesda, Maryland
• January 31, 2002

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Introduction
C

• Burkhard Daldrup, PhDGlobal Head, Drug
  Regulatory AffairsOncology Business Unit
• Novartis Pharmaceuticals Corporation

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ZOMETAOverview

• ZOMETA belongs to a new class of highly potent
  bisphosphonates
• Treatment of hypercalcemia of malignancy
• Approved by FDA in August 2001
• Approved in over 60 countries
• Treatment of bone metastases
• Filed July 2001 in EU and August 2001 in US and
  other major countries
• Dose Zoledronic acid 4 mg infused over 15 min q
  3 to 4 wk
• Non-oncologic uses under evaluation
• Pagets disease, osteoporosis, rheumatoid
  arthritis

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ZOMETA in Bone Metastases Proposed Indication

• ZOMETA (zoledronic acid) is indicated for the
  treatment of osteolytic, osteoblastic, and mixed
  bone metastases of solid tumors and osteolytic
  lesions of multiple myeloma, in conjunction with
  standard antineoplastic therapy

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ZOMETA in Bone MetastasesPhase III Trials
Three randomized, international, parallel,
double-blind trials
ZOMETA 4 mg and 8 mg PatientTrial
N versus
population Duration 010 1,648 Pamidronate Multiple
myeloma 13 mo Breast cancer 039
643 Placebo Prostate cancer 15 mo 011
773 Placebo Other solid tumors 9 mo
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ZOMETA in Bone MetastasesClinical Profile (1)

• ZOMETA is bone specific, not tumor specific
  effective in a broad variety of tumor types
  studied
• Breast cancer and multiple myeloma
• Prostate and other solid tumors
• Other bisphosphonates have not demonstrated
  efficacy in these tumor types

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ZOMETA in Bone MetastasesClinical Profile (2)

• First bisphosphonate shown to be effective across
  a wide variety of solid tumor types in treatment
  of bone metastases
• Safety is comparable with that of i.v.
  pamidronate
• Overall safety profile is supported by data from
  over 3,000 patients treated with ZOMETA

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Agenda

• Introduction . . . . . . . . . . . . . . . . . .
  . . . . . . . . . Burkhard Daldrup, PhD
• Pathophysiology of Metastatic Bone Diseaseand
  the Role of Bisphosphonates . . . . . . . . . .
  Prof. Robert Coleman, MD, FRCP
• ZOMETA in Breast Cancer and Multiple Myeloma .
  . . . . . . . . . . . . . . . . . . . . James
  Berenson, MD, Paul Gallo, PhD
• ZOMETA in Prostate Cancer and Solid Tumors
  Other Than Prostate Cancer
• and Breast Cancer . . . . . . . . . . . . . . . .
  . . . . . . . . . Matthew Smith, MD Prof. Robert
  Coleman,
• MD, FRCP
• Conclusions . . . . . . . . . . . . . . . . . .
  . . . . . . . . . . . David Parkinson, MD

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Questions and Answers

• Novartis Oncology
• Clinical Research and Development . . John
  Seaman, PharmD
• Consultants
• Statistics . . . . . . . . . . . . . . . . . . .
  . . . . . . . Richard J. Cook, PhD
• Thomas R. Fleming, PhD
• Clinical Experts
• Lung and Other Cancers . . . . . . . Pierre P.
  Major, MD, FRCPC
• Radiologic Analysis . . . . . . . . . Joseph F.
  Simeone, MD, FACR
• Renal Advisory Board . . . . . . . . . . Raimund
  R. Hirschberg, MD